Design,Synthesis, and Structure-Activity Relationship (SAR) Studies of Ketone-Isobenzofuranone Hybrid Herbicides

Thirty-five ketone-isobenzofuranone hybrids ( 1 – 35 ) were designed, synthesized, and evaluated for their herbicidal activity against Chinese amaranth (Amaranthus tricolor) and barnyard grass (Echinochloa crus-galli). The structure-activity relationship (SAR) results revealed that the position and type of substituent were crucial for activity. The o-substituted derivatives outperformed the m- and p-substituted derivatives. Compounds with strong electron-donating groups (OH, OMe) had low activity, while those with heterocycles (N-methylpyrrole, furan, and thiophene) had a moderate herbicidal effect. Compounds with a weak electron-donating group (Me) and weak, moderate, and strong electron-withdrawing groups (F, Cl, Br, and NO₂) showed promising herbicidal activity. Among these, the o-F substituted compound ( 20 ) was the most effective against Chinese amaranth, and the o-Cl substituted compound ( 23 ) was the most potent against barnyard grass. This is the first time the herbicidal potential of ketone-isobenzofuranone hybrids has been studied. The discovery of current chemical clues would be beneficial for the development of novel herbicides.     

Dihydroisocoumarins and phthalide from wood samples infested by fungi

Wood samples, infested by fungi during storage, were shown to contain, besides the known 5-methyl-mellein, additional (3R)-8-hydroxy-3-methyl-3,4-dihydroisocoumarins substituted by 7-methyl, 5-formyl, 5-carboxy, 5-hydroxy, 5-methoxy, 6-methoxy-5-methyl and 6,7-dimethoxy-5-methyl groups, as well as 6-formyl-7-hydroxy-5-methoxy-4-methylphthalide. Several 2-methylchromanones were synthesized in order to show that this class of compounds can be distinguished from 3-methyl-3,4-dihydroisocoumarins by MS.     

尼莫地平联合丁基苯酞对外伤性蛛网膜下腔出血患者脑微循环的影响

目的:探究尼莫地平联合丁基苯酞对外伤性蛛网膜下腔出血患者脑微循环的影响。方法:选取我院外伤性蛛网膜下腔出血患者36例,随机分为实验组和对照组,每组18例。对照组给予尼莫地平治疗,实验组给予尼莫地平联合丁基苯酞治疗。观察并比较两组患者治疗前后脑微循环的变化情况。结果:实验组总有效率(88.9%)高于对照组(61.1%),差异有统计学意义(P0.05);与治疗前相比,两组脑血容量(CBV)、脑血流量(CBF)水平均增高,平均通过时间(MTT)水平降低(P0.05);与对照组相比,实验组CBV和CBF水平较高,MTT较低(P0.05);与对照组相比,实验组格拉斯哥昏迷评分(GOS)评分较高、临床并发症发生率较低、6个月病死率较低,差异有统计学意义(P0.05)。结论:尼莫地平联合丁基苯酞可有效改善外伤性蛛网膜下腔出血患者的脑微循环,提高患者的生存率。     

Potential biofuel additive from renewable sources--Kinetic study of formation of butyl acetate by heterogeneously catalyzed transesterification of ethyl acetate with butanol

Butyl acetate holds great potential as a sustainable biofuel additive. Heterogeneously catalyzed transesterification of biobutanol and bioethylacetate can produce butyl acetate. This route is eco-friendly and offers several advantages over the commonly used Fischer Esterification. The Amberlite IR 120- and Amberlyst 15-catalyzed transesterification is studied in a batch reactor over a range of catalyst loading (6–12 wt.%), alcohol to ester feed ratio (1:3 to 3:1), and temperature (303.15–333.15 K). A butanol mole fraction of 0.2 in the feed is found to be optimum. Amberlite IR 120 promotes faster kinetics under these conditions. The transesterifications studied are slightly exothermic. The moles of solvent sorbed per gram of catalyst decreases (ethanol > butanol > ethyl acetate > butyl acetate) with decrease in solubility parameter. The dual site models, the Langmuir Hinshelwood and Popken models, are the most successful in correlating the kinetics over Amberlite IR 120 and Amberlyst 15, respectively.     

Generation of novel radiolabeled opiates through site-selective iodination

Tritiated opioid radioligands have proven valuable in exploring opioid binding sites. However, tritium has many limitations. Its low specific activity and limited counting efficiency makes it difficult to examine low abundant, high affinity sites and its disposal is problematic due to the need to use organic scintillants and its relatively long half-life. To overcome these issues, we have synthesized both unlabeled and carrier-free radioiodinated iodobenzoyl derivatives of 6β-naltrexamine (¹²⁵I-BNtxA, 18), 6β-naloxamine (¹²⁵I-BNalA, 19) and 6β-oxymorphamine (¹²⁵I-BOxyA, 20) with specific activities of 2100 Ci/mmol. To optimize the utility of the radioligand, we designed a synthesis in which the radiolabel is incorporated in the last synthetic step, which required the selective iodination of the benzoyl moiety without incorporation into the phenolic A ring. Competition studies demonstrated high affinity of the unlabelled compounds for opioid receptors in transfected cell lines, as did the direct binding of the ¹²⁵I-ligands to the opioid receptors. The radioligand displayed very high sensitivity, enabling a marked reduction in tissue, as well as excellent signal/noise characteristics. These new ¹²⁵I-radioligands should prove valuable in future studies of opioid binding sites.     

Prophylactic role of D-Saccharic acid-1,4-lactone in tertiary butyl hydroperoxide induced cytotoxicity and cell death of murine hepatocytes via mitochondria-dependent pathways

D-Saccharic acid 1,4-lactone (DSL) is a derivative of D-glucaric acid. It is a beta-glucuronidase inhibitor and possesses anticarcinogenic, detoxifying, and antioxidant properties. In the present study, the protective effects of DSL were investigated against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in vitro using murine hepatocytes. Exposure of TBHP caused a reduction in cell viability, enhanced the membrane leakage, and disturbed the intracellular antioxidant machineries in murine hepatocytes. Investigating the signaling mechanism of TBHP-induced cellular pathophysiology and protective action of DSL, we found that TBHP exposure disrupted mitochondrial membrane potential, facilitated cytochrome c release in the cytosol, and led to apoptotic cell death via mitochondria-dependent pathways. DSL counteracted these changes and maintained normalcy in hepatocytes. Combining, results suggest that DSL possesses the ability to ameliorate TBHP-induced oxidative insult, cytotoxicity, and apoptotic cell death probably due to its antioxidant activity and functioning via mitochondria-dependent pathways.     

Phthalides from the rhizome of Ligusticum wallichii

Three phthalides, 3-butylidene-7-hydroxyphthalide, and cis and trans-6,7-dihydroxyligustilides, along with a dimeric phthalide wallichilide have been isolated from the hot water extract of the rhizome of Ligusticum wallichii. Their structures were established mainly on the basis of spectroscopic data. 3-Butyl-4,5-dihydro-3-hydroxy phthalide and adenosine were identified as active principles of the extract which are responsible for increase of coronary blood flow in the dog heart.     

SDS‐PAGE‐free protocol for comprehensive identification of cytochrome P450 enzymes and uridine diphosphoglucuronosyl transferases in human liver microsomes

Comprehensive identification of cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs) in human liver microsomes (HLMs) was performed with an SDS‐PAGE‐free protocol. HLMs were solubilized with 5% v/v ionic liquid, 1‐butyl‐3‐methyl imidazolium tetrafluoroborate, followed by tryptic digestion, and 2D‐SCX‐RPLC‐ESI‐MS/MS (LTQ XL) analysis in triplicate. In total, 27 CYPs and 12 UGTs were confidently identified with average sequence coverage as 30.99 and 25.07%, average peptide number as 14 and 13, and average unique peptide number as 7 and 4, respectively. The highly similar isoforms of CYP3A, CYP2C, and CYP4F subfamilies could be unambiguously differentiated from each other, despite the fact that the sequence similarity of CYP2C9 and CYP2C19 is 91%. In addition, protein spectral count was used to approximately evaluate the relative abundance of identified CYPs and UGTs, and the results agreed with previous immunochemistry reports.     

Synthetic Racemate and Enantiomers of Cytosporone E,a Metabolite of an Endophytic Fungus,Show Indistinguishably Weak Antimicrobial Activity

The racemate and the enantiomers of cytosporone E [3-heptyl-4,5,6-trihydroxyphthalide (1)], a metabolite of the endophytic fungus, CR200 (Cytospora sp.), were synthesized. The key steps were (i) Sharpless asymmetric dihydroxylation of an alkene (8) and (ii) HPLC separation of the enantiomers of tert-butyldimethylsilyl ether (12) on a chiral stationary phase. The racemate and enantiomers of cytosporone E showed only weak antimicrobial activity with no difference among them.